This proposal describes a program to develop nanoparticles with advanced luminescence properties by combining zinc sulfide (ZnS) semiconductor nanoparticles and luminescent lanthanide cations so that the photophysical advantages of each are exploited. The aim is to use ZnS nanoparticles, with their large absorption cross section, to sensitize the lanthanide cations emission by an "antenna effect" and to provide a matrix that protects the lanthanides from nonradiative deactivation. ZnS is a desirable matrix because it is less toxic than the widely used CdSe nanocrystals, however the ZnS bandgap lies in the ultraviolet/blue spectral region, which has made them incompatible with biological imaging applications because of the strong interference between UV/blue photons and biological systems. However, the addition of lanthanide cations to the ZnS matrix causes the excitation energy to be released through the lanthanide cations as sharp emission bands in the visible and near infrared, determined by the nature of the lanthanide action. The lanthanide cations have sharp well defined emission bands that are insensitive to their environment (such as temperature, pH, pressure or biological environment) and allows for spectral discrimination from biological background (autofluorescence). Lanthanide cations also have longer luminescent lifetimes (micro- to milliseconds) than many other fluorescence emitters, allowing for temporal discrimination between the analyte signal and the background fluorescence. Chemical derivatization of the nanoparticle surface will be used to provide the biochemical selectivity for the nanocrystal probe and to make the material safe and soluble for the targeted biological applications. These materials will be tested in tissue and cell-based preparations and compared to commercially available probes for use in fluorescence microscopy applications. The toxicity of the nanocrystals will be evaluated using highly sensitive optical imaging methodologies for detecting cellular damage and death in primary cell culture models. PUBLIC HEALTH RELEVANCE: We will develop a novel family of luminescent nanoparticles that emit visible or near infrared light and are specifically designed to operate as fluorescent reporters in a broad range of "in vivo" and "in vitro" bioanalytical applications, including biological imaging. Ultimately, these nanoparticles will constitute a versatile luminescence platform whose optical properties will complement existing fluorophores, their signal being easily discriminated from the native fluorescence of biological systems.